Tyrosine kinase inhibitors are effective against solid tumors with activating mutations in tyrosine kinase gene, such as EGFR mutations or ALK fusion found in lung adenocarcinoma (NPL 1). We and other researchers have recently identified RET oncogene fusions in lung adenocarcinoma (NPL 2). This supports the importance of tyrosine kinase gene as a therapeutic target.
Meanwhile, inactivating somatic mutations in genes encoding chromatin-regulating protein subunits (e.g., histone acetyltransferases CBP/CREBBP and p300/EP300, histone methyltransferases MLL2 and SETD2, histone demethylases JARID1C and UTX, and chromatin remodeling factors BRG1, ARID1A, ARID2, PBRM1, and SNF5) have been largely attractive since they were first identified by the genome-wide sequencing analysis of cancer cells. These mutations are considered to inhibit functions in transcription or DNA double-strand break repair and thought to be crucial to the development and/or progression of cancer.
Unfortunately, therapeutic strategies for specifically targeting cancer cells having these mutations have not yet been developed.